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Modul.ting Wnt signal.ng to improve cel. repl.cement therapy for Parkinson＇s disease

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Journal.of Mol.cul.r Cel. Biol.gy 2014年第1期8卷 54-63页

作者： clare l. Parish l.chl.n H. Thompson Fl.rey Institute of Neuroscience and Mental.Heal.h The University of Melbourne Parkville VIC 3010 Australia

Cl.nical.trial. have demonstrated the capacity for dopamine neurons, transpl.nted ectopicaUy into the striatum, to structural.y inte- grate, restore dopamine transmission, and induce l.ng-term functional.benefits for Parkinson＇s disease （PD） patients. Despite this proof of principl., a number of l.mitations have hindered the devel.pment of cel. repl.cement therapy over the past 20 years, particu- l.rl. tissue avail.bil.ty, graft survival. and adequate reinnervation of the host brain. With a greater understanding of fail.re in prior cl.nical.trial., increased knowl.dge of midbrain dopamine devel.pment （now incl.ding Wnts）, and the devel.pment of pl.ripotent stem cel. technol.gies, we are better equipped than ever to re-address a number of these chal.enges. This review summarizes the trial., tribul.tions, and progress in cel. repl.cement therapy for PD. We discuss the prospects of modul.ting canonical.and non-canon- ical.Wnt signal.ngto improve cel. therapy based upon their rol.s in dopamine neural.devel.pment and the adul. brain. This wil. incl.de the potential.of Wnts to （i） expand fetaUy derived tissue in vitro and foUowing transpl.ntation, （ii） promote the differentiation of pl.ripotent stem cel.s, （iii） increase graft integration and restoration of neural.circuitry, and final.y （iv） enhance graft survival.

关键词： Wnt dopamine Parkinson's disease cel. transpl.ntation neurogenesis axon growth motor function

Tail.ring minimal.st sel.-assembl.ng peptides for l.cal.zed viral.vector aene del.verv

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Nano Research 2016年第3期9卷 674-684页

作者： Al.xandra l. Rodriguez Ting-Yi Wang Kiara F. Bruggeman Rui l. Richard J. Wil.iams clare l. Parish David R. Nisbet Research School.of Engineering The Australian National University Canberra ACT2601 Australia Fl.rey Institute ofNeuroscience & Men tal.Heal.h The University of Melbourne Parkville VIC 3010 Australia Cen tre for Chemistry and Biotechnol.gy Deakin University Waurn Ponds VIC 3217 Australia School.of Aerospace Mechanical and Manufacturing Engineering and the Health Innovations Research Institute RMIT University Melbourne VIC 300 I Australia

Viral.vector gene del.very is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings incl.ding brain and spinal.cord injury, as wel. as autoimmune diseases. Though promising resul.s have been demonstrated, l.mitations of viral.vectors, incl.ding spread of the virus to distant sites, neutral.zation by the host immune system, and l.w transduction efficiencies have stimul.ted the investigation of biomaterial. as gene del.very vehicl.s for improved protein expression at an injury site. Here, we show how N- fl.orenyl.ethyl.xycarbonyl.（Fmoc） sel.-assembl.ng peptide （SAP） hydrogel., designed for tissue-specific central.nervous system （CNS） appl.cations via incorporation of the l.minin peptide sequence isol.ucine-l.sine-val.ne-al.nine- val.ne （IKVAV）, are effective as biocompatibl., l.cal.zed viral.vector gene del.very vehicl.s in vivo. Through the addition of a C-terminal.l.sine （K） residue, we show that increased el.ctrostatic interactions, provided by the additional.amine side chain, al.ow effective immobil.zation of l.ntiviral.vector particl.s, thereby l.miting their activity excl.sivel. to the site of injection and enabl.ng focal.gene del.very in vivo in a tissue-specific manner. When the C-terminal.l.sine was absent, no difference was observed between the number of transfected cel.s, the vol.me of tissue transfected, or the transfection efficiency with and without the Fmoc-SAP. Importantl., immobil.zation of the virus onl. affected transfection cel. number and vol.me, with no impact observed on transfection efficiency. This hydrogel.al.ows the sustained and targeted del.very of growth factors post injury. We have establ.shed Fmoc-SAPs as a versatil. pl.tform for enhanced biomaterial.design for a range of tissue engineering appl.cations.

关键词： viral.vectors gene therapy sel.-assembl.ng peptides biomaterial.

Combined immunohistochemical.and retrograde tracing reveal. l.ttl. evidence of innervation of the rat dentate gyrus by midbrain dopamine neurons

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Frontiers in Biol.gy 2016年第3期11卷 246-255页

作者： Charl.tte M. Ermine Jordan l. Wright clare l. Parish Davor Stanic l.chl.n H. Thompson The Fl.rey Institute for Neuroscience and Mental.Heal.h The University of Melbourne Parkville Victoria 3010 Australia Current address Wol.son Institute for Biomedical.Research University College London Gower Street London WC1E 6BT UK

Al.hough the functional.neuroanatomy of the midbrain dopamine （mDA） system has been wel. characterized, the l.terature regarding its capacity to innervate the hippocampal.formation has been inconsistent. The l.ck of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has compl.cated studies in this area. Here we have used immunohistochemical.techniques to characterize the tyrosine hydroxyl.se expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The resul.s indicate that virtual.y al. tyrosine hydroxyl.se fibers throughout the hippocampus are of a noradrenergic phenotype, whil. the overl.ing cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustl. l.bel. tyrosine hydroxyl.se-immunoreactive noradrenergic neurons in the l.cus coerul.us but not mDA neurons.

关键词： noradrenal.ne hippocampus connectivity DAT neurogenesis

Dual.energy X-ray absorptiometry scans accuratel. predict differing body fat content in l.ve sheep

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Journal.of Animal.Science and Biotechnol.gy 2019年第1期10卷 248-253页

作者： David W Mil.er El.en J Bennett Joanne l.Harrison Fiona Anderson clare l.Adam School.of Veterinary and l.fe Sciences Murdoch University Scotl.nd’s Rural.Col.ege (SRUC) Peter Wilson Building The Facul.y of Heal.h University of Tasmania School.of Biol.gical.Sciences University of Aberdeen Rowett Institute of Nutrition and Heal.h University of Aberdeen

Background: There is considerabl. interest in impl.menting mobil. scanning technol.gy for on-farm body composition anal.sis on l.ve *** experiments eval.ated the use of dual.energy X-ray absorptiometry(DXA) as an accurate method of total.body fat measurement in l.ve ***: In Exp.1,visceral.and whol. body fat anal.sis was undertaken in sheep with body condition scores(BCS)in the range 2 to 3.25(scal. 1: thin to 5: fat).The rel.tionship of BCS was moderatel. correl.ted with visceral.fat depot mass(r = 0.59,P l. body fat(r = 0.70,P l.od sampl.d to anal.se circul.ting l.ptin concentrations,and were DXA scanned immediatel. post mortem for total.body *** l.ptin concentrations had l.w correl.tions with BCS(r = 0.50,P l.tion with chemical.body fat(r = 0.17,P > 0.05,n = 9).There was a moderate correl.tion between DXA body fat and BCS(r = 0.70,P l. correl.ted with chemical.body fat(r = 0.81,P l.,was performed on growing sheep over a 32-week *** average BCS ranged from 2.39 ± 0.07(S.E.M.) to 3.05 ± 0.11 and the DXA body fat(%) ranged from 16.8 ± 0.8 to 24.2 ± *** was a moderate correl.tion between DXA body fat and BCS over the 32 weeks(r = 0.61,P l.sions: Overal.,these experiments indicated that there was good agreement between BCS,DXA and chemical.anal.sis for measuring total.body fat in sheep,and that DXA scanning is a val.d method for l.ngitudinal.measurement of total.body fat in l.ve sheep.

关键词： BCS DEXA Fat l.ptin l.ngitudinal Sheep

Capturing the val.e of biosurveil.ance“big data”through natural.capital.accounting

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Big Earth Data 2021年第3期5卷 352-367页

作者： David Castl. Paul.D.N.Hebert El.zabeth l.clare Ian D.Hogg Crystal.Trembl.y School.Publ.c Administration and Gustavason School.of Business University of VictoriaCanada Centre for Biodiversity Genomics University of GuelphGuelphCanada Ecol.gy and Evol.tionary Biol.gy York UniversityTorontoCanada Ecosystem Science Polar Knowledge CanadaOttawa and Cambridge BayCanada Department of Geography University of VictoriaCanada

Gl.bal.biodiversity is in *** of the scal. and pace of biodiversity l.ss is l.ading to rapid technol.gical.devel.pment in biodiversity science to identify species,their interactions,and eco-system *** and international.pol.cy devel.pments to stimul.te mitigation and remediation actions are escal.ting to meet the biodiversity *** can take advantage of biosurveil.l.nce“big data”as evidence for more sweeping and impactful.pol.cy *** critical.factor is transl.ting biosurveil.ance data into the val.e-based frameworks underpinning new pol.cy *** approach to this integration process,using natural.capital.accounting frameworks is devel.ped.

关键词： Biodiversity biosurveil.ance big data SDGs pol.cy natural.capital.accounting digital.twins model.ing

Widening socioeconomic disparity in l.ng cancer incidence among men in New South Wal.s, Austral.a, 1987–2011

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Chinese Journal.of Cancer Research 2017年第5期29卷 395-401页

作者： Xue Qin Yu Qingwei l.o clare Kahn Camil.a Cahil. Marianne Weber Paul.Grogan Ahmedin Jemal.Dianne l.O'Connel. Cancer Research Division Cancer Council NSW Sydney School.of Publ.c Heal.h University of Sydney Sanofi Austral.a Cancer Council.Austral.a Surveil.ance and Heal.h Services Research American Cancer Society School.of Medicine and Publ.c Heal.h University of Newcastle

Objective：We assessed the trends in l.ng cancer incidence over a 25-year period by socioeconomic groups for men in New South Wal.s（NSW）,***：Men diagnosed with l.ng cancer between 1987 and 2011 were divided into five quintil.s according to an Index of Education and Occupation（IEO）.We assessed rel.tive socioeconomic differences over time by cal.ul.ting age-standardized incidence ratios（SIRs）by 5-year period of diagnosis,and estimated absol.te differences by comparing the observed and expected numbers of cases using the highest IEO quintil. as the ***：l.ng cancer incidence for men decreased from 1987 to 2011 for al. IEO quintil.s,with a greater rate of decl.ne for men l.ving in the highest IEO ***,the rel.tive disparity increased significantl. over the 25-year period（P=0.0006）.For exampl.,the SIR for the l.west IEO quintil. increased from 1.28 during 1987–1991 to 1.74during 2007–*** differences al.o increased with the proportion of＂potential.y preventabl.＂cases doubl.ng from 14.5% in 1987–1991 to 30.2% in 2007–***：Despite the overal. decl.ne in l.ng cancer incidence among men in NSW over the past 25 years,there was a significant increase in disparity across socioeconomic areas in both rel.tive and absol.te terms.

关键词： Austral.a l.ng cancer socioeconomic inequal.ty temporal.trends tobacco control.tobacco smoking

Social.interactions in a sol.tary carnivore

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Current Zool.gy 2017年第4期63卷 357-362页

作者： l. Mark El.ROCH Howard QUIGl.Y Panthera 8 West 40th Street 18th Floor New York NY 10018 USA

In total. 177 of 245 terrestrial.carnivores are described as sol.tary, and much of carnivore ecol.gy is buil. on the assumptions that interactions between adul. sol.tary carnivores are rare. We empl.yed Gl.bal.Positioning System （GPS） technol.gy and motion-triggered cameras to test predictions of l.nd-tenure territorial.ty and the resource dispersion hypothesis in a territorial.carnivore, the puma Puma concol.r. We documented 89 independent GPS interactions, 60% of which occurred at puma kil.s （n=53）, 59 camera interactions, 11 （17%） of which captured courtship behaviors, and 5 other interactions （1 F-F, 3 M-F, and 1 M-M）. Mean minimum weekl. contact rates were 5.5 times higher in winter, the season when el. Cervus el.phus were aggregated at l.wer el.vations and during which puma courtship primaril. occurred. In winter, contacts rates were 0.6_＋ 0.3 （standard devi- ation （SD）） interactions/week vs. 0.1 _＋ 0.1 （SD） interactions/week during summer. The preponder- ance of interactions at food sources supported the resource dispersion hypothesis, which predicts that resource fl.xes can expl.in temporary social.behaviors that do not resul. in any apparent benefits for the individual. invol.ed. Conspecific tol.rance is l.gical.when a prey is so l.rge that the predator that kil.ed it cannot consume it entirel., and thus, the costs of tol.rating a conspecific sharing the kil. are l.ss than the potential.costs associated with defending it and being injured. Puma aggregations at kil.s numbered as high as 9, emphasizing the need for future research on what expl.ins tol.rance among sol.tary carnivores.

关键词： carnivores competition Puma concol.r resource dispersion hypothesis social.interactions tol.rance.

Characterisation and risk assessment of venous thromboembol.sm in gastrointestinal.cancers

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Worl. Journal.of Gastrointestinal.Oncol.gy 2017年第9期9卷 363-371页

作者： Robert l.Metcal. Eamon Al.Hadithi Nichol.s Hopl.y Thomas Henry clare Hodgson Antony McGurk Wasat Mansoor Jurjees Hasan Department of Medical.Oncol.gy the Christie NHS Foundation Trust the University of Manchester Department of Biostatistics the Christie NHS Foundation Trust Department of Qual.ty and Standards the Christie NHS Foundation Trust

AIM To characterise venous thromboembol.sm(VTE) in gastrointestinal.cancer and assess the cl.nical.util.ty of risk stratification scoring. METHODS We performed a retrospective anal.sis using el.ctronic patient records of 910 gastro-oesophageal.GO) cancer and 1299 col.rectal.cancer(CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its rel.tionship to chemotherapy and impact on *** risk scores were cal.ul.ted using the Khorana index. Patients were cl.ssified as l.w risk(0 points), intermediate risk(1 to 2 points) or high risk(3 points). Data was anal.sed to determine the sensitivity of the Khorana score to predict VTE. RESUl.S The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pul.onary embol.(PE) were more common in advanced than in l.cal.sed CRC(50% vs 21% of events respectivel.) and l.wer l.mb deep vein thrombosis(DVT) were more common in l.cal.sed than in advanced CRC(62% vs 39% of events respectivel.). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In l.cal.sed CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in l.cal.sed disease and 6.8 mo in advanced disease. No survival.difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had l.w or intermediate Khorana risk score(94% for l.cal.sed and 97% in advanced CRC). In GO cancer, al. patients scored either intermediate or high risk due to the primary site demonstrating a l.mitation of the risk assessment score in discriminating high and l.w risk patients with GO cancers. Additional.risk factors were identified in this cohort incl.ding surgery, chemotherapy or hospital.admission. Overal., 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These shoul.

关键词： Thrombo-embol.sm Deep venous thrombosis Pul.onary embol.sm Col.rectal.cancer Oesophageal.cancer Gastro-oesophageal.cancer

Drug therapy for heart fail.re in ol.er patients —what do they want？

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Journal.of Geriatric Cardiol.gy 2015年第2期12卷 165-173页

作者： Donah Zachariah Jacquel.ne Tayl.r Nigel.Rowel. clare Spooner Paul.R Kal.a Portsmouth Hospital. NHS Trust Portsmouth P06 3L Y UK Gl.sgow Royal.Infirmary Glasgow G40SF UK South Tees Hospital. NHS Foundation Trust TS4 3BW UK Servier l.boratories l.d SL3 6P J UK

Chronic heart fail.re （CHF） is predominantl. seen in ol.er patients, and therefore real.l.fe medicine often requires the extrapol.tion of findings from trial. conducted in much younger popul.tions. Prescribing patterns and potential.benefits in the el.erl. are heavil. infl.enced by pol.pharmacy and co-morbid pathol.gies. Increasing l.ngevity may become l.ss rel.vant in the frail.el.erl., whereas improving qual.ty of l.fe （Qol. often becomes priority; the onus being on improving wel.being, maintaining independence for l.nger, and del.ying institution- al.sation. Specific studies eval.ating el.erl. patients with CHF are l.cking and l.ttl. is known regarding the tol.rabil.ty and side-effect profil. of evidence based drug therapies in this popul.tion. There has been recent interest on the impact of heart rate in patients with symptomatic CHF. Ivabradine, with sel.ctive heart rate l.wering capabil.ties, is of benefit in patients with CHF and l.ft ventricul.r systol.c dysfunction in sinus rhythm, resul.ing in reduction of heart fail.re hospital.sation and cardiovascul.r death. This manuscript wil. focus on CHF and the ol.er patient and wil. discuss the impact of heart rate, drug therapies and tol.rabil.ty. It wil. al.o highl.ght the tmmet need for specific studies that focus on patient-centred study end points rather than mortal.ty targets that characterise most therapeutic trial.. An on-going study eval.- ating the impact of ivabradine on Qol.that presents a unique opportunity to eval.ate the tol.rabil.ty and impact of an establ.shed therapy on a wide range of real.l.fe, ol.er patients with CHF wil. be discussed.

关键词： Heart fail.re Heart rate Qual.ty of l.fe The el.erl.